Some forms of cancer are caused by DNA mutations that “turn on” oncogenes (genes that speed up cell division) or “turn off” tumor suppressor genes (genes that slow down cell division or cause cells to die at the right time). In people with non-Hodgkin’s lymphoma (NHL), these mutations are normally acquired after birth. The mutations may occur from exposure to radiation or cancer-causing chemicals, but many times the mutations occur for no apparent reason. Researchers have noted that these mutations seem to appear more often as people grow older. Age is the greatest risk factor for NHL, with more than half of the cases occurring in people over age 65. 

A mutation type that can cause NHL is a translocation. A translocation is the transfer of DNA from one chromosome to another. This abnormality can turn on oncogenes or turn off tumor suppressor genes.

In addition, the immune system appears to play a significant role in many cases of lymphoma. People with immune deficiencies are at an increased risk of developing the disease. This population can include patients with HIV infection and congenital immune deficiencies, as well as those who have undergone organ transplants. 

Although these factors may explain some cases of NHL, researchers do not yet understand how the disease develops in people with no apparent risk factors.